Selective Interaction of Syntaxin 1A with KCNQ2: Possible Implications for Specific Modulation of Presynaptic Activity
dc.contributor.author | Regev, Noa | |
dc.contributor.author | Degani-Katzav, Nurit | |
dc.contributor.author | Korngreen, Alon | |
dc.contributor.author | Etzioni, Adi | |
dc.contributor.author | Siloni, Sivan | |
dc.contributor.author | Alaimo Campi, Alessandro ![]() | |
dc.contributor.author | Chikvashvili, Dodo | |
dc.contributor.author | Villarroel Muñoz, Álvaro | |
dc.contributor.author | Attali, Bernard | |
dc.contributor.author | Lotan, Ilana | |
dc.date.accessioned | 2019-03-08T16:19:23Z | |
dc.date.available | 2019-03-08T16:19:23Z | |
dc.date.issued | 2009-08-13 | |
dc.identifier.citation | PLOS ONE 4(8) : (2009) // e6586 | es_ES |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/10810/31946 | |
dc.description.abstract | KCNQ2/KCNQ3 channels are the molecular correlates of the neuronal M-channels, which play a major role in the control of neuronal excitability. Notably, they differ from homomeric KCNQ2 channels in their distribution pattern within neurons, with unique expression of KCNQ2 in axons and nerve terminals. Here, combined reciprocal coimmunoprecipitation and two-electrode voltage clamp analyses in Xenopus oocytes revealed a strong association of syntaxin 1A, a major component of the exocytotic SNARE complex, with KCNQ2 homomeric channels resulting in a similar to 2-fold reduction in macroscopic conductance and similar to 2-fold slower activation kinetics. Remarkably, the interaction of KCNQ2/Q3 heteromeric channels with syntaxin 1A was significantly weaker and KCNQ3 homomeric channels were practically resistant to syntaxin 1A. Analysis of different KCNQ2 and KCNQ3 chimeras and deletion mutants combined with in-vitro binding analysis pinpointed a crucial C-terminal syntaxin 1A-association domain in KCNQ2. Pull-down and coimmunoprecipitation analyses in hippocampal and cortical synaptosomes demonstrated a physical interaction of brain KCNQ2 with syntaxin 1A, and confocal immunofluorescence microscopy showed high colocalization of KCNQ2 and syntaxin 1A at presynaptic varicosities. The selective interaction of syntaxin 1A with KCNQ2, combined with a numerical simulation of syntaxin 1A's impact in a firing-neuron model, suggest that syntaxin 1A's interaction is targeted at regulating KCNQ2 channels to fine-tune presynaptic transmitter release, without interfering with the function of KCNQ2/3 channels in neuronal firing frequency adaptation. | es_ES |
dc.description.sponsorship | This work was supported by the Israeli Science Foundation (ISF) grants no. 208/06 (I.L.), 1396/05) (I.L.) and 672/05 (B.A.); The Public Committee for Allocation of Estate Funds grant no. 3-4181, Ministry of Justice, Israel (I.L.); The Israel Ministry of Science 'Tashtiot' program and a DFG-DIP grant (B. A.); the Spanish Ministry of Education grant no. SAF2006-13450 (A.V.) and the Consolider project CSD2008-00005 (A.V.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Public Library Science, | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | transmembrane conductance regulator | es_ES |
dc.subject | KCNQ2/KCNQ3 K+ channels | es_ES |
dc.subject | CA1 pyramidal cells | es_ES |
dc.subject | C-terminal domains | es_ES |
dc.subject | potassium channels | es_ES |
dc.subject | neuronal excitability | es_ES |
dc.subject | surface expression | es_ES |
dc.subject | open probability | es_ES |
dc.subject | xenopus-oocyte | es_ES |
dc.title | Selective Interaction of Syntaxin 1A with KCNQ2: Possible Implications for Specific Modulation of Presynaptic Activity | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2009 Regev et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0006586 | es_ES |
dc.identifier.doi | 10.1371/journal.pone.0006586 | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |
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Except where otherwise noted, this item's license is described as © 2009 Regev et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.